1-204229029-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014935.5(PLEKHA6):​c.2659G>A​(p.Gly887Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

PLEKHA6
NM_014935.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47
Variant links:
Genes affected
PLEKHA6 (HGNC:17053): (pleckstrin homology domain containing A6)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16611713).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLEKHA6NM_014935.5 linkuse as main transcriptc.2659G>A p.Gly887Arg missense_variant 19/23 ENST00000272203.8 NP_055750.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLEKHA6ENST00000272203.8 linkuse as main transcriptc.2659G>A p.Gly887Arg missense_variant 19/231 NM_014935.5 ENSP00000272203 P2
PLEKHA6ENST00000637508.1 linkuse as main transcriptc.3031G>A p.Gly1011Arg missense_variant 23/275 ENSP00000490182 A2
PLEKHA6ENST00000414478.1 linkuse as main transcriptc.2719G>A p.Gly907Arg missense_variant 19/235 ENSP00000402046

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251432
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461862
Hom.:
0
Cov.:
33
AF XY:
0.0000261
AC XY:
19
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 29, 2021The c.2659G>A (p.G887R) alteration is located in exon 19 (coding exon 17) of the PLEKHA6 gene. This alteration results from a G to A substitution at nucleotide position 2659, causing the glycine (G) at amino acid position 887 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.028
T;T;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.79
T;T;T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.17
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;.;.
MutationTaster
Benign
0.98
D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.19
N;.;N
REVEL
Benign
0.13
Sift
Benign
0.11
T;.;T
Sift4G
Benign
0.23
T;.;T
Polyphen
1.0
D;.;.
Vest4
0.49
MutPred
0.18
Gain of solvent accessibility (P = 0.0674);.;.;
MVP
0.068
MPC
0.28
ClinPred
0.25
T
GERP RS
5.4
Varity_R
0.037
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372056044; hg19: chr1-204198157; API